Complement Receptor type 3 (CR2) is the receptor for the d fragment of the third component of human complement. CR2 is also the receptor for Epstein-Barr virus, a human herpes virus which causes acute infectious mononucleosis and polyclonal B-cell lymphomas and is associated with African Burkitt's lymphoma and nasopharygeal carcinoma. CR2 is expressed on B-lymphocytes during those stages of B-cell differentiation important for reception and transduction of antigenic signals and is felt to play a role in the B-cell activation process. B lymphocyte expression of CR2 is reduced in patients with systemic lupus erythematosus. Trisomy of the complement regulatory protein locus to which CR2 maps has been associated with several myeloproliferative disorders. A putative murine complement receptor which reacts with a rabbit antibody to the purified human receptor has been identified. The apparent molecular weight of the murine antigen, its cellular distribution and ligand specificity, suggest that it is murine CR2. During the first three years of this proposal, this protein will be purified and characterized with the development of monospecific reagents. The gene for this putative murine CR2 will be cloned and sequenced. The ontogeny of receptor expression, and its role in B-cell activation will be studied using inbred mouse strains with known abnormalities of B-cell regulation. Comparison of the human and murine receptor should provide insight into the different structural requirements for EBV and C3d attachment.